LEOPARD syndrome:: Clinical diagnosis in the first year of life

LEOPARD syndrome (LS) is all autosomal dominant syndrome charcterised by multiple lentigines and cafe-au-lait spots, electrocardiographic-conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormalities of the genetalia in males, retardation of growth and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in PTPN11, a gene encoding the protein tryosine phosphate SHP-2 located at chromosomes 12q22qter. The clinical diagnosis of LS is generally different in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A PTPN11 gene mutation was detected in 8/10 (80%) patients. In one patient without a PTPN11 mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, Who had previously Undiagnosed classic NF1. The age of LS patients with PTPN11 mutation ranged between I and I I months (mean age +/- SD 7.5 +/- 3.96 months). Review of the clinical characteristics of patients with LS confirmd by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age call be clinically suspected in patients presenting with three main features, that is, characteristic facial features (1000/6), hypertrophic cardiomyopathy (HCM) (87%), and cafe-au-lait spots (75%). Characteristic facial features Call be Mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for PTPN11 mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling. (c) 2006 Wiley-Liss, Inc.